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Role of probiotics Lactobacillus reuteri and Lactobacillus rhamnosus on the inflammatory profile and renin angiotensin system in an experimental model of chronic stress

Grant number: 21/05331-1
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): April 01, 2022
Effective date (End): March 31, 2026
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Tatiana de Sousa da Cunha Uchiyama
Grantee:Lívia Bruni de Souza
Host Institution: Instituto de Ciência e Tecnologia (ICT). Universidade Federal de São Paulo (UNIFESP). Campus São José dos Campos. São José dos Campos , SP, Brazil
Associated research grant:17/17027-0 - Hormonal systems in renal and cardiovascular diseases: from cell biology to new physiological paradigms with advances for therapeutics, AP.TEM


Stress is one of the most significant health problems in modern society and can be defined as any change in homeostasis, which requires an adaptive response. Due to limitations inherent to research with human beings, animal models have been very useful in the study of the physiological mechanisms underlying the deleterious effects triggered by stress. Although it is been established that rodents adapt to repetitive stressful stimuli, this adaptation does not occur in methods of Chronic Unpredictable Mild Stress (CUMS), where alternating exposure to different stressor stimuli, for approximately 3 consecutive weeks, inducing continuous elevation of continuous levels of corticosterone and alteration of glycemic and lipid metabolism, observed up to 15 days after the application of the last stressor stimulus. It has been established the Renin-Angiotensin System (RAS) acts in important mechanisms such as blood pressure control, extracellular volume, and tissue perfusion. In this system, the Angiotensin Converting Enzyme (ACE), converts angiotensin I into a potent peptide vasopressor (angiotensin II) and inactivates a potent vasodilator (bradykinin). In previous studies, we demonstrated that ECMI induced interstitial and perivascular fibrosis in cardiac tissue, and the treatment with angiotensin II AT1 blocker (losartan) attenuated the development of these changes. In addition to it is important role in the development of cardiac fibrosis, angiotensin II appears to worsen dysbiosis, increasing permeability, and intestinal inflammation. In this scenario, probiotics has also been used in order to minimize stress and harmful effects on different systems. Probiotics are dietary supplements, consisted of bacteria, with vast colonizing power in the gastrointestinal tract and offering systemic benefits to the host, with potential anti-inflammatory effect. Therefore and considering that: 1) the number of people affected by complications resulting from chronic stress is increasing; 2) cardiovascular dysfunction due to stress is associated with high rates of cardiac injury and mortality; 3) stress triggers RAS activation, favoring the pro-inflammatory events; 4) increased angiotensin II, contributing to intestinal permeability; 5) probiotics have a potential beneficial effect, favoring metabolic balance, preventing adverse cardiovascular events and repairing the intestinal barrier, this study aims to evaluate the role of chronic administration of probiotics Lactobacillus rhamnosus and Lactobacillus reuteri, on cardiometabolic changes due to of chronic stress, seeking a new therapeutic option for this disorder, and understanding of the pathways that are modulated by this resource. (AU)

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